Follow-Up Data from UCSF Suggests Cyberknife Monotherapy Results Improved Slightly Over Time

Original Study Compared Stereotactic Monotherapy, Boost and Brachytherapy

by John Otrompke

(c) 2011 John Otrompke

Follow-up analysis from a small study comparing boost and monotherapy with the Cyberknife and brachytherapy for prostate cancer suggests that some monotherapy results have improved since publication, a researcher from the University of California at San Francisco said.

In the original study, published last year in the International Journal of Radiation Oncology, Biology and Physics, 20 of 38 patients were treated by the Cyberknife with stereotactic radiotherapy as a monotherapy, while 18 received the Cyberknife treatment as a boost (following external beam radiation and hormone therapy). 

The article, ‘Stereotactic Body Radiotherapy as Monotherapy or Post-External Beam Radiotherapy Boost for Prostate Cancer: Technique, Early Toxicity, and PSA Response’ (Jabbari, et al), which was published December 21, 2010, reported results at a minimum follow-up of 12 months.

In the time since publication (nearly a year), PSA nadirs for those treated with Cyberknife monotherapy have come down to more closely approach the lower level achieved with patients who received Cyberknife therapy as a boost. PSA nadir for those who received boost therapy was 0.3 nanograms per milliliter upon follow-up analysis, compared to about 0.5 at the time of the original publication,according to Alexander R. Gottschalk, MD, PhD, associate professor in radiation oncology at the University of California at San Francisco, a co-author on the study.

The nadir for those treated with both external beam radiation and the Cyberknife remains at 0.1, he added.

To date, Gottschalk has treated about 110 patients with stereotactic therapy, about half with monotherapy, and half as a boost, he said. In the study, which was not randomized, sicker patients received Cyberknife as a boost, Gottschalk explained.

“Patients who got Cyberknife treatment as a boost also received hormonal therapy, because in general they had more advanced disease, which required more aggressive therapy,” he said. “I try to choose whether they should get monotherapy or boost therapy depending on their prostate cancer characteristics,” he added.

Those who received Cyberknife as a monotherapy received 9.5 Gray for four fractions, while those who received a boost received the same dose for two fractions. When stereotactic therapy was used as a boost, the patients got 25 fractions of conventional radiation with two fractions of SBRT.

At the time of the study, researchers compared the PSA nadir achieved with both forms of Cyberknife treated with that experienced in a similar group of 44 patients who received brachytherapy, or high dose rate radiation with temporary radioactive “seeds,” according to the study.

Those in the monotherapy cohort had a median PSA nadir of 0.47 in the originally-published data, compared to 0.1 in the cohort which received boost therapy. 

For those who received brachytherapy, the nadir was 0.09, with a median follow-up of 48.6 months, the study indicated.

There are two types of brachytherapy: a permanent implant, and high dose rate radiation, in which a patient usually stays in the hospital for about 24 hours, Gottschalk noted.

Follow-up data indicated that grade three gastro-intestinal side effects remained the same and late grade three gastro-urinary toxicities remained similar.

In the original study, 42% of patients who received monotherapy with the Cyberknife had acute Grade 2 toxicity, compared to 11% of those who received Cyberknife as a boost, at a median follow-up of 18.3 months.

While Gottschalk still reported no early-occurring grade three gastrointestinal toxicities, about four out of 110 patients have reported a late-occurring grade three gastro-urinary toxicity, requiring a catheterization, he said.

In the original study, two patients experienced a late-occurring grade three gastro-urinary toxicity. Biochemical and clinical data show that no patients have progressed, Gottschalk added.

MR Editorial Advisor Tang Attends Conference with Taiwanese President

by John Otrompke

MR’s editorial advisor, Prof. Hsiao-Wei Tang, PhD, was honored to appear and speak at a conference along with the president of Taiwan, Ma Ying-Jeou. 

The Invest in Taiwan forum is an event focusing on minimally-invasive surgery technology, said Tang, who is also the director of the International Center of Excellence in Medical Robot at the Asian Institute of Telesurgery,  http://aits.tw/ , in Taiwan.

Tang is hopeful for progress with his developmental robotic device, the Hua Tuo robot, which will be publicly demonstrated on phantoms in Taipei, Taiwan, this month. 

The prior incarnation of the robot, the Vesalius, was developed with funding from the University of Leuven, Belgium, which stopped development last year. Taiwanese surgeon Dr. Min-Ho Huang, who has funded hospitals and research centers, convinced Tang to move the project to Taipei, and now he and colleagues have developed a second iteration, the Hua Tuo Robot.

“The IP belongs to the University of Leuven. Now they are preparing to sign the the memorandum of understanding with me. Although they own the IP, I have all the know-how in my brain,” Tang explained.

The new version, which was developed at a cost of about $50,000 US, is more compact, and its position is more adjustable, according to Tang. The prior version weighed about eleven kilograms. Tang also said be hopes one advantage of a Taiwanese-made device would be its affordability- less than $12,000, Tang speculated.

Following the demonstration of the device as a camera holder in the robotic surgery context, at Chiang Kai Shek Memorial Hall on November 20, Tang will depart for     another research engagement at Stanford University, he said.

 

Joint Working Group of Standards Organizations Meets to Define Medical Robotics

by John Otrompke

A joint working group of two standards-setting organizations, the International Standardization Organization (ISO), and the International Electrotechnical Commission (IEC), met in Nuremberg, Germany for the second time last month to establish definitions for medical robots, as another step in creating standards for the design and manufacture of the devices.

While medical robots are thought as a preliminary matter to include aids for the disabled, as well as those which perform invasive and non-invasive procedures such as surgery, rehabilitation therapy, imaging and other robots for medical diagnosis and treatment, a number of theoretical issues remain undetermined, according to Gurvinder S. Virk, PhD, who chairs the entity, which is known as joint working group nine.

Distinctions in terminology could be important, according to Virk, who is also a professor of robotics at the University of Gävle in Sweden. “Up to now, robots have been classified as machines, and are therefore governed by machinery directive, established by the European Union.” 

Among other categories include personal care robots, which an an individual uses to help himself or herself without any kind of medical connotations, Virk added. “Some devices, such as assistant exoskeletons such as a device called E-Legs which is available in the U.S., or the HAL (hybrid assistive limb), by the Japanese company Cyberdyne, help old people move about, but the medical people on our committee say that getting old is not a medical issue.”

Virk is also the founder of CLAWAR, the association of Climbing and Walking Robots, which is incorporated in the UK.

“What’s the difference between medical equipment and a medical robot?” Virk asked. “It seems to me to be autonomy, whereas most medical equipment in current use does not have any autonomous functions.”

The distinctions can become thorny, according to Virk. “The da Vinci is able to filter out the tremor of the surgeon, and most people would argue that that’s an autonomous capability.” However, the FDA license for the da Vinci describes the device as an endoscope, not a robot, according to Virk.

The joint working group will next meet in February of 2012, in Orlando. Virk and colleagues are also planning an annual International Colloquium on Medical Robots, to be held next July in Milan, Italy.

Multiple Training Systems Under Study at the University of Nebraska

by John Otrompke

Follow-up research is underway to validate a surgical training module used in-house at the University of Nebraska. The training method has already demonstrated improvements in speed and smoothness of movement, according to a paper recently published in the International Journal of Medical Robotics and Computer-Assisted Surgery.

Following the most recent publication, researchers are validating the results with a larger trial.  “Right now we’re in the middle of about 25 subjects, and hopefully we’ll get about 50 students students and fellows,” said Dr. Joseph Ka-Chun Siu, PhD, assistant professor in the College of Public Health. The current study will look at retention of skills six months following training, he said.

The training program, which is in its fifth year, has trained about 30 individuals in da Vinci surgery, using an interface provided by Intuitive and a custom LabView program manufactured by National Instruments out of Concord, Massachusetts.

The training program uses a technique called Augman video feedback, in which participants can either watch their performance in real time or obtain quantitative measures of fast they perform surgical procedures such as suturing, Siu said. The institution purchased the commercial LabView software about ten years ago for about $1,000, according to Siu, and subsequently customized the software, because “the robot has no direct communication back to the surgeon, saying how well you do in this procedure,” Siu explained.

        Improvement in Some Measures, While Others Remain Enigmatic

   In the training program, 15 medical students with no prior robotic surgery experience went through a four-day training program followed by a retention test a day later, according to the article (“,Training program for fundamental surgical skill in robotic laparoscopic surgery,” Suh, Mukherjee, Oleynikov and Siu). 

Prior to the retention test, the average score measured by the Objective standardized assessment of technical skills (OSATS) criteria was 43.1%, but it increased to 66.4% after the training, and 74.1% at the time the retention test was administered, the paper said. 

The students averaged 25 years; 12 were male,  and three female. Researchers also examined the activities of the flexor carpi radialis and extensor digitorum, two muscles in the forearm that have been associated with surgical fatigue, and found that fatigue was reduced following the training program.

“We’re not going to strengthen the muscles, but rather to see how much muscle effort they use in order to complete the task,” explained Siu, who noted that the paper reported about a 30% reduction in fatigue following the training program.

Researchers found the simulator improved a measure called ‘movement curvature,’ a measure of “whether you move the robot in a smooth fashion,” according to Siu.

All students were right-handed. There were no significant differences in terms of the total distance traveled in performing the surgical procedures studied, the paper said. A prior randomized study of ten volunteers (“A Virtual Reality Training Program for Improvement of Robotic Surgical Skills,” Mukherjee, Siu, et al, Studies in Health Technology and Informatics, 2009), found that improvements in total distance traveled enjoyed by students who used a virtual reality simulator disappeared when students used their non-dominant arm. However, that study involved a virtual reality program, not the LabView module, according to Siu.

                         Bountiful Training Modules

Another early study from 2008 (“Validated robotic laparoscopic surgical training in a virtual-reality environment,” Katsavelis, Siu, et al, Surgical Endoscopy, 2008), noted the desirability of increasing the complexity of the virtual reality training environment.

“To increase the complexity of the tasks, we are increasing the steps for the participant to complete. That first report involved very simple tasks like bimanual carrying and needle passing, but right now we use the mesh alignment task, a procedure that people commonly use to repair a hernia, which requires multiple steps in order to complete,” Siu explained.

Another change from the earlier papers is that the virtual reality training program now uses a program called Vizart, manufactured by Worldviz, instead of the Webots program used initially.

“Worldlviz gives us more degrees of freedom, because the virtual object is written in a simple language, so that we can write it by ourself. Provide syntax so we can modify it with drop-down menus,” Siu said.

Regarding the module used in the training program, which incorporates the Labview product, but not the virtual reality simulator, Siu said the institution has not yet sold the product to anybody, although the studies have shown that 80 to 90% of participants improve their surgical skills. “We just use that one as our in-house training program. We did not have a good communication with the company” regarding commercialization, because Intuitive still has ownership of the platform, he explained.

Accordingly, the institution is also developing its own training simulator, which does not use the LabView product, he said.

Endocontrol Hoping for Year of Development

Japanese Marketing Approval Sought for ViKY, as 

Device is Used for the First Time in Taiwan 

by John Otrompke


   Endocontrol, a company based in Grenoble, France, is hoping for a year of successful developments, as the company recently submitted an application for marketing approval in Japan for its leading device, ViKY. 


   Elsewhere, a Taiwanese surgeon performed the first procedure with the device in Taiwan, and the company is hoping to release the world’s first five millimeter motorized needle driver in 2011. 


   Endocontrol submitted the application to market the Vision Kontrol Endoscopy device (ViKY) in Japan in February of this year, according to Stephen Song, MBA, vice president for sales and marketing. 


   Over 1,000 procedures have been performed with the ViKY since it came on the market in 2008. The ViKY is approved in Canada, the European Union, Korea, Russia, Taiwan, and the U.S., Song added.


                                              Useful in Gynecologic Procedures


   In April of this year, the ViKY was used for the first time in Taiwan by Dr. Yih-Huei Uen, who used a wireless microphone to control the movement and position of the laparoscope during a single incision laparoscopic cholecystectomy, or gall bladder removal, at Chi-Mei Medical Center in Tainan.


   The ViKY is especially useful in gynecologic procedures, such as hysterectomy and gynecologic reconstruction, according to Song, performed either with or without the da Vinci. Those procedures are performed with uterine manipulator, which is an instrument inside the uterus, used as a handle to move the uterus around, or as a vaginal dilator, he said.


   “The da Vinci cannot do it, because the architecture of the arms will not allow an arm to get into that position,” said Song, adding that the ViKY can be controlled either by voice, or by a foot pedal on the floor.


   The ViKY can also be used for single port surgeries, in which it controls the laparoscopic telescope that goes through the access device, and in transrectal natural orifice transluminal endoscopic surgeries (NOTES), Song said.


                              Smaller Motorized Devices May Lead to Better Outcomes 


   In addition, the company anticipates releasing the world’s first five millimeter motorized instrument, a needle driver, during 2011, Song added.


   The device, the JAiMY (Jaime Articulating Instrument Motorized endoscopY), which is named after the primary engineer on the project, is also reusable, according to Song.


   Most instruments are currently ten millimeters in size. “But the smaller the diameter of the device, the smaller the incision that must be made to accommodate it into the body. Smaller incisions mean less pain, scarring, disfigurement and less chance of developing an abdominal wall hernia,” which currently occur with an incidence between 1 to 6% in ports that are larger than 10 millimeters, according to the literature, according to Song, who noted that the JAiMY is designed for use in any laparoscopic procedure, with or without the ViKy.

Trials on UCLA’s Robotic Training Device Postponed

Meanwhile, Researchers at Work on Other Robotic Developments 


by John Otrompke

Work on one of several medical robots under design at the University of California at Los Angeles has reached the point of human trials, but the trials were delayed until the fall, according to an administrator at the Center for Advanced Surgical and Interventional Technology (CASiT).

“We’re just finishing up the final touches on optimization systems and network connections on one of our projects, called the Laprobot,” said Erik Dutson, MD, coordinator of CASiT. “This robot would not need to go to the FDA; it would train them to do laparoscopies and minimally invasive surgery, which is now required to become a general surgeon,” he said.

The current incarnation is actually the second iteration of the Laprobot, according to Dutson. “We made it from scratch. The first platform was not as robust, so we remachined a lot of parts so they function more consistently,” he said, adding that UCLA manufactured every piece of the device, except the motor.

Once the tests begin, Dutson and colleagues will begin experimenting with novices. “We’re going to run them through three  of five standardized tests, to see if can teach them at a faster rate with a robotic interface,” said Dutson. The researchers would   test the Laprobot on three groups of ten novices, and use the device to teach them to pass a plastic triangle from one hand to another without dropping it. to do a surgical knot, and thirdly, a  scissor cut, he explained.

Initially, the experiments were to be complete by the end of the summer, but they have now been postponed until October or November, according to an administrator, so that researchers could resolve network issues and not have a problem with video delays in the telesurgery project.

“The robot would have to have certified as validated training tool, so we would request their endorsement of the Society for American Gastrointestinal Endoscopic Surgeons (SAGES),” Dutson said. If successful, he would hope to market the device for about $100,000 apiece, he added.

Other Research, Including Novel Robot for Eye Surgery

However, the Laprobot is only one of several project under way at the institution. A second one is a modular system under design for adding tactile feedback to surgical robots, while the other is a novel robot designed for eye surgery, Dutson said.

“We have patented a system which registers tactile feedback to the da Vinci, which allows us to mount silicon balloon pads that cause pressure indentations on the fingertips.

The system is modular, according to Dutson, which means that it could be remodulated for any other potential surgical robot, should another large manufacturer decide to produce one.

“One of issues with the system is whether it’s too expensive, or whether the water-proofing is cost effective,” said Dutson, noting that each instrument for a da Vinci costs around $2,500 and may last for ten uses. Adding the tactile feedback system may add another $500 or $1,000 per instrument, according to Dutson, who added that marketing is probably at least two years in the future.

A more novel product under design is a robot for opthalmalogic surgery. 

“The platform for this is fundamentally different from any former surgical robot,” said Dutson. “The da Vinci has a series of arms for a modular platform that rolls over the patient, while the platform for  our opthalmologic robot is a halo which is secured to the patient’s bed over their head, allowing it to operate relative to the bony structures in the skull,” he added.

Having co-authored an early paper on robotic ocular surgery (“Robotic Ocular Surgery,” by Tsirbas, Dutson, and Mango, in the British Journal of Opthalmology,  January of 2007), Dutson and fellow researchers Tsu-Chin Tsao, PhD, professor in the department of mechanical and aerospace engineering, and Jean-Pierre Hubschman, MD, an assistant professor in Jules Stein Eye Institute, have made a smaller robot for retinal surgery.